Since the beginning of antiquity, both pharmacy and medicine have sought a delivery system for administering a beneficial drug. The first written reference to a dosage form is the Eber Papyrus, written about 1552 B.C. The Eber Papyrus mentions dosage forms such as anal suppositories, vaginal pessaries, ointments, oral pill formulations, and other dosage preparations. About 2500 years passed without any advance in dosage form development, when the Arab physician Rhazes, 865-925 A.D., invented the coated pill. About a century later the Persian Avicenna, 980-1037 A.D., coated pills with gold or silver for increasing patient acceptability and for enhancing the effectiveness of the drug. Also around this time, the first tablet was described in Arabian manuscripts written by al-Zahrawi, 936-1009 A. D. The manuscripts described a tablet formed from the hollow impressions in two facing tablet molds. Pharmacy and medicine waited about 800 years for the next innovation in dosage forms, when in 1883 Mothes invented the capsule for administering drug. The next quantum leap in dosage forms came in 1972 with the invention of the osmotic delivery device by inventors Theeuwes and Higuchi. The osmotic delivery device is manufactured in one embodiment for oral use, and in this embodiment it embraces the appearance of a tablet with a drug delivery portal. It is the first oral dosage form that delivers a given amount of drug per unit time at a controlled and known rate of delivery over a prolonged period of time.
Also, since the beginning of antiquity, pharmacy and medicine considered it desirable to prescribe pharmaceutical dosage forms containing at least two different drugs for obtaining the pharmacological benefits of each drug. The coadministration of certain drugs is prescribed often in fixed ratios for several reasons. For example, for drugs that have the same therapeutic effect but act mechanistically different on the body, such combinations may have the added therapeutic effect of both agents but less side effects, or the drugs may act synergistically and create a larger than additive effect. Also, drug combinations are prescribed for treatments where each individual drug addresse different symptoms of a particular medical situation. Although, a large number of therapeutic combinations could be provided, often they can not be compounded in the same dosage form because each drug needs to be administered on a different schedule. The different schedule is needed because each drug has a different biological half life and therapeutic index and therefore each drug should be administered in separate dosage forms on a prescribed schedule that is specific for each drug. Thus, a drug that needs to be administered four times a day, should not be combined with a drug that should be administered once a day. These drugs are kinetically incompatible in a pharmaceutical dosage form. Another reason why certain drugs cannot be combined is they may be chemically incompatible or unstable in the presence of each other. This kinetic or chemical incompatibility can be eliminated by the novel dosage form provided by this invention. For example, by using the dosage form provided by this invention, a regimen consisting of four times a day administration of drug can be transformed into a once a day administration such that the drug previously administered four times daily can be combined with a drug administered once daily. In other words, both drugs can be coadministered to the body at delivery rates that are matched to achieve each of their separate therapeutic plasma concentrations. Thus, in the light of the above presentation, it will be appreciated by those versed in the dispensing art, that if an improved delivery system is made available for housing a drug or two or more different drugs for independent or for simultaneous independent codelivery, at continuous and controlled rates in therapeutically effective amounts for obtaining the benefits of each drug, such a delivery system would have a definite use and be a valuable contribution to the dispensing arts. The present invention advances the state of the dispensing art by making available a delivery system housing a number of osmotic delivery devices each having an independent delivery portal for increasing the bioavailability of the drug, the dispersion of drug in a drug receiving environment and concomitantly decreasing the likelihood of local unwanted effects, and for dispensing at least one drug, or at least two different drugs to a biological receptor substantially-free of interaction and drug incompatibility.